Relationship between cyclooxygenase activity (COA) inhibition and stimulation of ventilation by salicylate.
Recent investigations have demonstrated that inhibition of the cyclooxygenase enzyme of the prostaglandin synthetase complex accounts for most of the pharmacological effects of salicylate. To determine whether inhibition of cyclooxygenase activity (COA) plays a role in stimulation of ventilation (VE) by salicylate, sodium salicylate and other more potent inhibitors of COA (i.e., indomethacin and ibuprofen) were infused into anesthetized dogs. These experimental intravascular infusions lasted 1 hr; VE and oxygen consumption (VO2) were continuously measured. In the initial series of experiments, all COA inhibitors were infused at a rate of 25 mumol/kg/min. It was noted that only salicylate elicited consistent increases in either VE or VO2. The possibility that high infusion rates of potent COA inhibitors may prevent stimulation of VE by some additional toxic effect was explored in a second series of experiments in which we infused the minimal amount of COA inhibitors necessary to completely inhibit cyclooxygenase in other experimental situations. In these experiments, it was noted that none of the COA inhibitors (i.e., salicylate, meclofenamate, indomethacin or ibuprofen) stimulated either VE or VO2. These observations suggest that salicylate stimulates VE by a mechanism other than inhibition of prostaglandin synthetase. Because salicylate-induced increases in VE and VO2 followed a similar time course, these results are consistent with our concept that stimulation of VE by salicylate is related to tissue hypermetabolism.
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D062385:Hydroxybenzoates / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D012119:Respiration / Q000187:drug effects*; D012459:Salicylates / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D012980:Sodium Salicylate / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D062385:Hydroxybenzoates; D012459:Salicylates; C032948:3-hydroxybenzoic acid; D012965:Sodium Chloride; D012980:Sodium Salicylate; D007052:Ibuprofen; D007213:Indomethacin